Lamotrigine (All indications)

Oro-facial clefts

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S15197
R62330		 Cohen (Lamotrigine) (Mixed indications), 2023 Orofacial clefts 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Partial overlapping 0.84 [0.50;1.42] -/8,339   -/4,866,362 - 8,339
ref
S10035
R40890		 Blotière (Lamotrigine) (Mixed indications), 2019 Oro-facial clefts 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 0.89 [0.33;2.37] C 4/2,997   2,815/1,875,733 2,819 2,997
ref
S8971
R30402		 Dolk (Lamotrigine) (Mixed indications), 2016 Isolated orofacial cleft 1st trimester case control unexposed (general population or NOS) Adjustment: Yes 1.46 [0.76;2.80] -/-   0/ - -
ref
S8908
R30102		 Källén (Lamotrigine) (Indications NOS), 2013 Orofacial cleft early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Partial overlapping 2.14 [0.58;5.48] 4/1,084   2,756/1,575,847 2,760 1,084
ref
S8921
R30156		 Holmes (Lamotrigine), 2008 All isolated (Cleft palate alone, Cleft lip alone and Cleft lip and palate) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 10.40 [4.30;24.90] 5/684   145/206,224 150 684
ref
Total 5 studies 1.85 [0.77;4.43] 5,729 13,104
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF Cohen (Lamotrigine) (Mixed indications), 2023Cohen, 2023 1 0.84[0.50; 1.42]-8,33923%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Blotière (Lamotrigine) (Mixed indications), 2019Blotière, 2019 2 0.89[0.33; 2.37]2,8192,99719%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Dolk (Lamotrigine) (Mixed indications), 2016Dolk, 2016 3 1.46[0.76; 2.80]--22%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Källén (Lamotrigine) (Indications NOS), 2013Källén, 2013 4 2.14[0.58; 5.48]2,7601,08417%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Holmes (Lamotrigine), 2008Holmes, 2008 5 10.40[4.30; 24.90]15068420%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 84% 1.85[0.77; 4.43]5,72913,1040.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Lamotrigine) (Mixed indications; 2: Lamotrigine) (Mixed indications; 3: Lamotrigine) (Mixed indications; 4: Lamotrigine) (Indications NOS; 5: Lamotrigine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.99[0.59; 6.67]5,72913,10488%NACohen (Lamotrigine) (Mixed indications), 2023 Blotière (Lamotrigine) (Mixed indications), 2019 Källén (Lamotrigine) (Indications NOS), 2013 Holmes (Lamotrigine), 2008 4 case control studiescase control studies 1.46[0.76; 2.80]-- -NADolk (Lamotrigine) (Mixed indications), 2016 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.85[0.77; 4.43]5,72913,10484%NACohen (Lamotrigine) (Mixed indications), 2023 Blotière (Lamotrigine) (Mixed indications), 2019 Dolk (Lamotrigine) (Mixed indications), 2016 Källén (Lamotrigine) (Indications NOS), 2013 Holmes (Lamotrigine), 2008 5 Tags Adjustment   - No  - No 3.07[0.28; 34.20]2,9693,68193%NABlotière (Lamotrigine) (Mixed indications), 2019 Holmes (Lamotrigine), 2008 2   - Yes  - Yes 1.20[0.72; 1.99]2,7609,42335%NACohen (Lamotrigine) (Mixed indications), 2023 Dolk (Lamotrigine) (Mixed indications), 2016 Källén (Lamotrigine) (Indications NOS), 2013 3 Partial overlappingPartial overlapping 1.17[0.49; 2.81]2,7609,42354%NACohen (Lamotrigine) (Mixed indications), 2023 Källén (Lamotrigine) (Indications NOS), 2013 2 All studiesAll studies 1.85[0.77; 4.43]5,72913,10484%NACohen (Lamotrigine) (Mixed indications), 2023 Blotière (Lamotrigine) (Mixed indications), 2019 Dolk (Lamotrigine) (Mixed indications), 2016 Källén (Lamotrigine) (Indications NOS), 2013 Holmes (Lamotrigine), 2008 50.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.82.80.6870.000Cohen (Lamotrigine) (Mixed indications), 2023Blotière (Lamotrigine) (Mixed indications), 2019Dolk (Lamotrigine) (Mixed indications), 2016Källén (Lamotrigine) (Indications NOS), 2013Holmes (Lamotrigine), 2008

Asymetry test p-value = 0.3880 (by Egger's regression)

slope=-1.0507 (1.5115); intercept=4.0370 (4.0080); t=1.0072; p=0.3880

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.85[0.77; 4.43]5,72913,10484%NACohen (Lamotrigine) (Mixed indications), 2023 Blotière (Lamotrigine) (Mixed indications), 2019 Dolk (Lamotrigine) (Mixed indications), 2016 Källén (Lamotrigine) (Indications NOS), 2013 Holmes (Lamotrigine), 2008 50.510.01.0